Sleeve Gastrectomy Increases Colitis-Associated Colon Tumor Growth Independent of Diet

Abstract

INTRODUCTION: We have previously found that sleeve gastrectomy (SG) causes increased numbers of tumors in a diet-induced obesity mouse model of colitis-associated cancer (CAC). Here we examine the effects of SG on CAC in lean mice fed a regular diet. METHODS: Twelve-week-old lean C57BL/6J mice were maintained on a normal chow diet and randomized to SG or sham operation. Five weeks postoperatively, CAC was established via one-time injection of azoxymethane (AOM) followed by 2-week-long periods of dextran sulfate sodium (DSS) administration. Colitis severity was scored from 0 to 12 by measuring weight loss, stool consistency, and hematochezia. The number of colonic tumors and total tumor surface area were measured at sacrifice 46 days after DSS and compared using Welch’s t-test. RESULTS: CAC tumors were significantly larger in lean SG mice compared with sham (0.67 cm2 vs 0.29 cm2; p = 0.046; Figs. 1A, 1B). However, lean SG mice developed similar levels of colitis as sham (maximum colitis severity 4.7 vs 4.1; data not shown) and similar numbers of tumors (4.4 vs 3.6; p = 0.61; Fig. 1C). In contrast, in obese mice, SG leads to increased tumor numbers (5.5 vs 1.4; p = 0.0003; Fig. 1D) as well as increased colitis severity and larger tumors (data not shown).Figure 1CONCLUSION: SG increases tumor size in a mouse CAC model independent of diet and obesity. SG-induced increases in tumor number and colitis severity are present in diet-induced obese but not lean mice. These data suggest that surgery, diet, and obesity have distinct roles in colon cancer initiation and growth.